Abstract
Trichuriasis is a disease of poverty for which excretory and secretory (ES) products that induce the protective immunity are being investigated as candidate vaccines antigens. In this study, ES products of T. muris and immune sera were produced. The immune sera recognized more than 20 proteins on a 2D-gel of ES products of T. muris adult worms. Tm16 was one of the proteins identified by mass spectrometry. Tm16 shares 57% sequence identity with Ov16, an immunodominant diagnostic antigen from Onchocerca volvulus. Recombinant Tm16 with a carboxyl terminal hexahistidine was produced using Pichia pastoris. Polyclonal antibodies against rTm16 were generated by one-prime and two-boost immunization of three female Balb/c mice with 25 μg of recombinant Tm16 emulsified with ISA720 adjuvant. These polyclonal antibodies confirmed that Tm16 is localized to the ES products and the soluble fraction of the adult worm. Additionally, the high-resolution crystal structure of Tm16 was solved by molecular replacement. Tm16 belongs to the phosphatidylethanolamine-binding-like protein (PEBP1) family and this is the first structure of a PEBP1 from a parasite.
Highlights
Trichuris trichiura, one of the three most common soiltransmitted nematodes, causes trichuriasis in more than 450 million people and an estimated 544,000 disability adjusted life years globally according to the Global Burden of Disease Study 2015 [1]
The T. muris excreted products were separated on 2D gel and visualized with Coomassie staining (Figure 1(a)) or probed with mouse anti-excretory and secretory (ES) immune sera (Figure 1(b))
The crystal structure of Tm16 is the first structure of a parasite phosphatidylethanolamine-binding-like protein (PEBP) and reveals a prototypical phosphatidylethanolamine-binding-like topology with a large binding cavity capable of accommodating various ligands and suggestive of the ability to bind with macromolecules related to the signal pathway and transduction or cell migration and regulation (Figures 4 and 5)
Summary
One of the three most common soiltransmitted nematodes, causes trichuriasis in more than 450 million people and an estimated 544,000 disability adjusted life years globally according to the Global Burden of Disease Study 2015 [1]. The current approaches for soil-transmitted helminth infections such as trichuriasis include mass drug administration, but the major drugs (mebendazole, albendazole) used to treat trichuriasis have a low (28–36%) cure rate [5] and do not completely break the cycle of reinfection [6] This observation explains why the global prevalence of human whipworm infection has decreased only 2.1% over the last decade [1], such that there is a vital need for alternative therapies that ameliorate the health of infected people in order to alleviate the global health and economic and social burdens of NTDs. Currently, trichuriasis is diagnosed using fecal egg counts and there is a need to develop additional diagnostic methods
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